Recent research endeavors have established that the mechanochemical activation of piezoelectric materials can open new avenues in redox chemistry. Impact forces, such as those imparted by a ball ...mill, have been shown to transform piezoelectric materials such as barium titanate (BaTiO3) into a highly polarized state, which can then donate an electron to a suitable oxidant and receive an electron from a suitable reductant, mimicking established photoredox catalytic cycles. Proof‐of‐concept studies have elucidated that mechanoredox chemistry holds great potential in sustainable and efficient radical‐based synthesis.
The application of mechanical force to a material can lead to the generation of electric charge; piezoelectricity. For the first time, this effect has been harnessed and applied to radical reactions under ball‐milling conditions, this Concept briefly describes the first appearances of this ground‐breaking technique in the literature.
Resetting of the epigenome in human primordial germ cells (hPGCs) is critical for development. We show that the transcriptional program of hPGCs is distinct from that in mice, with co-expression of ...somatic specifiers and naive pluripotency genes TFCP2L1 and KLF4. This unique gene regulatory network, established by SOX17 and BLIMP1, drives comprehensive germline DNA demethylation by repressing DNA methylation pathways and activating TET-mediated hydroxymethylation. Base-resolution methylome analysis reveals progressive DNA demethylation to basal levels in week 5–7 in vivo hPGCs. Concurrently, hPGCs undergo chromatin reorganization, X reactivation, and imprint erasure. Despite global hypomethylation, evolutionarily young and potentially hazardous retroelements, like SVA, remain methylated. Remarkably, some loci associated with metabolic and neurological disorders are also resistant to DNA demethylation, revealing potential for transgenerational epigenetic inheritance that may have phenotypic consequences. We provide comprehensive insight on early human germline transcriptional network and epigenetic reprogramming that subsequently impacts human development and disease.
Display omitted
•SOX17-BLIMP1 with TFCP2L1 and KLF4 constitute a unique hPGC transcriptome•hPGC transcriptome drives extensive DNA demethylation and chromatin reorganization•Evolutionarily young and hazardous retrotransposons remain partially methylated•Some demethylation resistant loci are candidates for epigenetic inheritance
A unique transcriptome drives extensive epigenome resetting in human primordial germ cells for establishment of totipotency. Some loci associated with metabolic and neurological disorders exhibit resistance to reprogramming and are candidates for transgenerational epigenetic inheritance.
The construction of diverse sp3‐rich skeletal ring systems is of importance to drug discovery programmes and natural product synthesis. Herein, we report the photocatalytic construction of ...2,7‐diazabicyclo3.2.1octanes (bridged 1,3‐diazepanes) via a reductive diversion of the Minisci reaction. The fused tricyclic product is proposed to form via radical addition to the C4 position of 4‐substituted quinoline substrates, with subsequent Hantzsch ester‐promoted reduction to a dihydropyridine intermediate which undergoes in situ two‐electron ring closure to form the bridged diazepane architecture. A wide scope of N‐arylimine and quinoline derivatives was demonstrated and good efficiency was observed in the construction of sterically congested all‐carbon quaternary centers. Computational and experimental mechanistic studies provided insights into the reaction mechanism and observed regioselectivity/diastereoselectivity.
Building bridges: The reductive photocatalytic dearomatization of quinoline derivatives using N‐arylimines is described. The bridged 1,3‐diazepane architecture is constructed through the addition of an intermediary α‐amino radical to the C4‐position of a 4‐substituted quinoline and subsequent reductive cyclization.
The para‐selective C−H alkylation of aniline derivatives furnished with a pyrimidine auxiliary is herein reported. This reaction is proposed to take place via an N−H‐activated cyclometalate formed in ...situ. Experimental and DFT mechanistic studies elucidate a dual role of the ruthenium catalyst. Here the ruthenium catalyst can undergo cyclometalation by N−H metalation (as opposed to C−H metalation in meta‐selective processes) and form a redox active ruthenium species, to enable site‐selective radical addition at the para position.
Para‐normal activity: The para‐selective C−H alkylation of aniline derivatives is reported. The methodology is proposed to proceed by a dual role ruthenium process: cycloruthenation at N−H and redox radical generation. This strategy leads to para‐selective alkylations using pyrimidine and quinazoline auxiliaries.
PDF
